The broad objectives of the proposed study are to investigate regulatory mechanisms which modulate the development and spread of epileptiform activity following application of a chemical epileptogenic agent to cerebral cortex; to study the interactions between cerebellum and cerebral cortex during various states of seizure activity; to correlate cerebellar effects of antiepileptic drugs with possible mechanisms of action; to pursue the development of laboratory models useful in the identification of new compounds with possible antiepileptic utility; to continue to access the hypothesis that compounds which act to limit the spread of epileptiform activity may exert this effect through reinforcement of cerebellar inhibitory mechanisms; and to examine potential mechanisms to explain the development of hyperexcitability in cerebral cortex following injury or disease. These objectives will be achieved through recordings of cerebellar Purkinje cell discharge, cerebral cortical epileptiform activity, and cortical DC potentials in cats with epileptiform foci. Modification of these parameters by cerebellar-stimulant antiepileptic agents and by various brain stem and spinal lesions will contribute to an understanding of the mechanisms involved in the development and transmission of cortical hyperexcitability and seizure discharge. In addition, mechanisms underlying the clinical utility and toxicity of antiepileptic compounds will be delineated.